Microglial Cystatin F Expression Is a Sensitive Indicator for Ongoing Demyelination With Concurrent Remyelination
Microglial Cystatin F Expression Is a Sensitive Indicator for Ongoing Demyelination With Concurrent Remyelination
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DOI：
10.1002/jnr.22567
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发表时间：
2011-05-01
影响因子：
4.2
通讯作者：
Ikenaka, Kazuhiro
中科院分区：
文献类型：
--
作者：
Ma, Jianmei;Tanaka, Kenji F.;Ikenaka, Kazuhiro
脱髓鞘与中枢神经系统（CNS）基因表达的许多变化一致。半胱抑素F是一种木瓜蛋白酶样溶酶体半胱氨酸蛋白酶抑制剂，通常由免疫细胞表达，而不是在大脑中表达，在急性脱髓鞘过程中在中枢神经系统中大量诱导。我们发现，中枢神经系统中的单核/巨噬细胞系小胶质细胞仅在脱髓鞘过程中表达胱抑素F。采用多种脱髓鞘动物模型和多发性硬化症（MS）脊髓组织，采用原位杂交和免疫组织化学方法检测胱抑素F的时空表达模式。我们发现胱抑素F诱导的时间与正在进行的脱髓鞘相匹配，并且胱抑素F表达的地方与脱髓鞘区重叠。最有趣的是，慢性脱髓鞘中胱抑素F的诱导停止，脱髓鞘再生能力丧失。这些发现表明，胱抑素F的表达表明正在发生脱髓鞘/再脱髓鞘，而胱抑素F表达的缺失表明脱髓鞘区域的再脱髓鞘已经停止。(C) 2011 Wiley-Liss, Inc。
Demyelination coincides with numerous changes of gene expression in the central nervous system (CNS). Cystatin F, which is a papain-like lysosomal cysteine proteinase inhibitor that is normally expressed by immune cells and not in the brain, is massively induced in the CNS during acute demyelination. We found that microglia, which are monocyte/macrophage-lineage cells in the CNS, express cystatin F only during demyelination. By using several demyelinating animal models and the spinal cord tissues from multiple sclerosis (MS) patients, we examined spatiotemporal expression pattern of cystatin F by in situ hybridization and immunohistochemistry. We found that the timing of cystatin F induction matches with ongoing demyelination, and the places with cystatin F expression overlapped with the remyelinating area. Most interestingly, cystatin F induction ceased in chronic demyelination, in which remyelinating ability was lost. These findings demonstrate that the expression of cystatin F indicates the occurrence of ongoing demyelination/remyelination and the absence of cystatin F expression indicates the cessation of remyelination in the demyelinating area. (C) 2011 Wiley-Liss, Inc.